Radiation exposure causes hepatitis which induces hepatic steatosis and fibrosis. Although hepatic stellate cells (HSCs) have been considered potential pathological modulators for the development of hepatitis due to viral and microbial infections, their involvement in radiation-induced hepatitis is yet to be determined. This study aimed to clarify the relationship between radiation exposure and expressions of inflammatory cytokines and chemokines in HSCs in vitro and in vivo. HSCs were obtained from 1-week-old mice, known to be highly sensitive to radiation-induced hepatocellular carcinoma, using a newly established method combining liver perfusion, cell dissociation, and density gradient centrifugation, followed by magnetic negative selection of hematopoietic and endothelial cells with anti-CD45.2 and CD146 antibodies. The isolated HSCs were confirmed by the expression of desmin and glial fibrillary acidic protein (GFAP). We demonstrated that primary cultured HSCs, exposed to X-ray irradiation (0, 1.9, and 3.8 Gy) and cultured for 3 and 7 days, produced elevated levels of C-C motif chemokine ligand 5 (CCL5, also known as RANTES) inflammatory chemokine in a dose-dependent manner. An in vivo immunofluorescence method confirmed that increased CCL5 signals were observed in GFAP-positive HSCs in mouse livers 7 days after whole-body X-ray irradiation (1.9 and 3.8 Gy). Adequate expression of C-C motif chemokine receptor 5 (Ccr5), a receptor for CCL5, was also detected using real-time PCR in the liver of both irradiated and non-irradiated mice. Taken together, our data suggest that HSCs may drive hepatitis via CCL5/CCR5 axis in the liver under radiation-induced stress. Furthermore, this newly established experimental protocol can help evaluate the expression of other inflammatory cytokines in primary cultures of HSCs isolated from infant mice.
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Research Article|
October 25 2024
Hepatic Stellate Cell-mediated Increase in CCL5 Chemokine Expression after X-ray Irradiation Determined In Vitro and In Vivo
Masataka Taga;
Masataka Taga
1
aDepartment of Molecular Biosciences, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima City, Hiroshima, Japan
1Address for correspondence: Department of Molecular Biosciences, Radiation Effects Research Foundation; email: [email protected].
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Kengo Yoshida;
Kengo Yoshida
aDepartment of Molecular Biosciences, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima City, Hiroshima, Japan
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Shiho Yano;
Shiho Yano
aDepartment of Molecular Biosciences, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima City, Hiroshima, Japan
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Keiko Takahashi;
Keiko Takahashi
aDepartment of Molecular Biosciences, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima City, Hiroshima, Japan
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Seishi Kyoizumi;
Seishi Kyoizumi
aDepartment of Molecular Biosciences, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima City, Hiroshima, Japan
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Megumi Sasatani;
Megumi Sasatani
bDepartment of Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan
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Keiji Suzuki;
Keiji Suzuki
cRadiation Risk Control Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
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Tomohiro Ogawa;
Tomohiro Ogawa
dCenter for the Advancement of Higher Education, Faculty of Engineering, Kindai University, Osaka, Japan
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Yoichiro Kusunoki;
Yoichiro Kusunoki
aDepartment of Molecular Biosciences, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima City, Hiroshima, Japan
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Tatsuaki Tsuruyama
Tatsuaki Tsuruyama
aDepartment of Molecular Biosciences, Radiation Effects Research Foundation, 5-2 Hijiyama Park, Minami-ku, Hiroshima City, Hiroshima, Japan
eDepartment of Drug and Discovery Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
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Radiat Res (2024)
Article history
Received:
June 30 2023
Accepted:
October 16 2024
Citation
Masataka Taga, Kengo Yoshida, Shiho Yano, Keiko Takahashi, Seishi Kyoizumi, Megumi Sasatani, Keiji Suzuki, Tomohiro Ogawa, Yoichiro Kusunoki, Tatsuaki Tsuruyama; Hepatic Stellate Cell-mediated Increase in CCL5 Chemokine Expression after X-ray Irradiation Determined In Vitro and In Vivo. Radiat Res 2024; doi: https://doi.org/10.1667/RADE-23-00127.1
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